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Biomedical subjects

M Rundgren

Publications and source records attributed to M Rundgren.

At least 19 recordsLinked to original sources

Activation of central opioid receptors determines the timing of hypotension during acute hemorrhage-induced hypovolemia in conscious sheep.

After an initial compensatory phase, hemorrhage reduces blood pressure due to a widespread reduction of sympathetic nerve activity (decompensatory phase). Here, we investigate the influence of intracerebroventricular naloxone (opioid-receptor antagonist) and morphine (opioid-receptor agonist) on the two phases of hemorrhage, central and peripheral hemodynamics, and release of vasopressin and renin in chronically instrumented conscious sheep. Adult ewes were bled (0.7 ml x kg(-1) x min(-1)) from a jugular vein until mean arterial blood pressure (MAP) reached 50 mmHg. Starting 30 min before and continuing until 60 min after hemorrhage, either artificial cerebrospinal fluid (aCSF), naloxone, or morphine was infused intracerebroventricularly. Naloxone (200 microg/min but not 20 or 2.0 microg/min) significantly increased the hemorrhage volume compared with aCSF (19.5 +/- 3.2 vs. 13.9 +/- 1.1 ml/kg). Naloxone also increased heart rate and cardiac index. Morphine (2.0 microg/min) increased femoral blood flow and decreased hemorrhage volume needed to reduce MAP to 50 mmHg (8.9 +/- 1.5 vs. 13.9 +/- 1.1 ml/kg). The effects of morphine were abolished by naloxone at 20 microg/min. It is concluded that the commencement of the decompensatory phase of hemorrhage in conscious sheep involves endogenous activation of central opioid receptors. The effective dose of morphine most likely activated mu-opioid receptors, but they appear not to have been responsible for initiating decompensation as 1) naloxone only inhibited an endogenous mechanism at a dose much higher than the effective dose of morphine, and 2) the effects of morphine were blocked by a dose of naloxone, which, by itself, did not delay the decompensatory phase.

Acute Disease↗

Training methods for horses: habituation to a frightening stimulus.

REASONS FOR PERFORMING STUDY: Responses of horses in frightening situations are important for both equine and human safety. Considerable scientific interest has been shown in development of reactivity tests, but little effort has been dedicated to the development of appropriate training methods for reducing fearfulness. OBJECTIVES: To investigate which of 3 different training methods (habituation, desensitisation and counter-conditioning) was most effective in teaching horses to react calmly in a potentially frightening situation. HYPOTHESES: 1) Horses are able to generalise about the test stimulus such that, once familiar with the test stimulus in one situation, it appears less frightening and elicits a reduced response even when the stimulus intensity is increased or the stimulus is presented differently; and 2) alternative methods such as desensitisation and counter-conditioning would be more efficient than a classic habituation approach. METHODS: Twenty-seven naive 2-year-old Danish Warmblood stallions were trained according to 3 different methods, based on classical learning theory: 1) horses (n = 9) were exposed to the full stimulus (a moving, white nylon bag, 1.2 x 0.75 m) in 5 daily training sessions until they met a predefined habituation criterion (habituation); 2) horses (n = 9) were introduced gradually to the stimulus and habituated to each step before the full stimulus was applied (desensitisation); 3) horses (n = 9) were trained to associate the stimulus with a positive reward before being exposed to the full stimulus (counter-conditioning). Each horse received 5 training sessions of 3 min per day. Heart rate and behavioural responses were recorded. RESULTS: Horses trained with the desensitisation method showed fewer flight responses in total and needed fewer training sessions to learn to react calmly to test stimuli. Variations in heart rate persisted even when behavioural responses had ceased. In addition, all horses on the desensitisation method eventually habituated to the test stimulus whereas some horses on the other methods did not. CONCLUSIONS AND POTENTIAL RELEVANCE: Desensitisation appeared to be the most effective training method for horses in frightening situations. Further research is needed in order to investigate the role of positive reinforcement, such as offering food, in the training of horses.

Animals↗

Circulatory effects of angiotensin II during anaesthesia, evaluated by real-time spectral analysis.

BACKGROUND: General anaesthesia may stimulate the renin-angiotensin system. Exogenous administration of angiotensin II elevates blood pressure mainly via increased total peripheral resistance caused by direct vasoconstrictor actions. It is also well established that the hypertensive effect of angiotensin II involves a cerebrally mediated component. The hypertensive effect of an intravascular infusion of angiotensin II is substantially reduced by isoflurane anaesthesia. A likely mechanism is that isoflurane anaesthesia reduces the cerebral component of the angiotensin II effect on blood pressure, which involves influences on autonomic nervous activity. In an experimental study in sheep we used real-time spectral analysis of arterial blood pressure signals to obtain information on parasympathetic, respectively, sympathetic autonomic nervous activity in response to angiotensin II administration during isoflurane anaesthesia. METHODS: The study was performed on conscious and isoflurane-anaesthetized sheep that were subjected to an intracarotid infusion of angiotensin II (85 ng kg(-1) min(-1)) during 20 min followed by a recovery period of 30 min and thereafter an injection of the angiotensin II, AT1-receptor antagonist losartan (10 mg kg(-1)) i.v. Systemic and regional (renal and femoral) circulation was monitored in parallel to real-time spectral analysis of the arterial blood pressure signal. RESULTS: Isoflurane anaesthesia reduced both magnitude and duration of the hypertensive response to angiotensin II infusion. The power spectral density in the frequency band that represents sympathetic activation, correlated to the changes in mean arterial pressure in conscious animals, but not during isoflurane anaesthesia. CONCLUSION: We conclude that the cerebrally mediated component of the hypertensive effect of circulating angiotensin II is largely eliminated by isoflurane anaesthesia. Spectral power analysis of the blood pressure signal indicates that the cerebral angiotensin II effect involves activation of sympathetic nervous activity.

Anesthesia↗

Responses of horses in behavioural tests correlate with temperament assessed by riders.

REASONS FOR PERFORMING STUDY: Behavioural tests as well as observers' ratings have been used to study horses' temperament. However, the relationship between the ratings and the responses in behavioural tests has not yet been studied in detail. OBJECTIVES: The aim of the present study was to examine this relationship between ratings and responses. METHODS: Eighteen mature Swedish Warmblood horses were subjected to 2 behavioural tests, one relating to novelty (novel object test) and one to handling (handling test). Subsequently, 16 of these horses were ridden by 16 equally experienced students, having no former experience with the horses. Immediately after each ride, the students scored the horse for 10 temperamental traits using a line rating method. RESULTS: It was shown that for each temperamental trait all 16 riders agreed on the ranking of the horses (0.212<W<0.505, P < 0.001). CONCLUSIONS: Correlations between behavioural and heart rate variables in the behavioural tests revealed that horses with a high level of locomotion or much restlessness behaviour exhibited high mean heart rate and low heart rate variability. In particular, heart rate variables in the behavioural tests were found to correlate with riders' rating scores. Furthermore, the underlying components of the handling test, retrieved with a principal component analysis (PCA) correlated with riders' rating scores while the underlying components of the novel object test did not. POTENTIAL CLINICAL RELEVANCE: It is concluded that it is possible for a large panel of assessors to agree upon a horse's temperament and that objective measures from behavioural tests correlate significantly with temperamental traits assessed by a panel of assessors.

Adult↗

Repeatability and validity of a combined mail and telephone questionnaire on demographics, diet, exercise and health status in an insured-dog population.

The validity and repeatability of a telephone questionnaire on demographics, diet, living patterns, exercise and health status in a well-defined dog population was assessed. Randomly selected dogs aged 1-3 years in the largest animal-insurance database of Sweden were included in the study. The repeatability was measured by doing two identical interviews with 64 dog owners on average 39 (S.D. 17) days apart. The overall response percentage was 66% (64/97). The repeatabilities for demographic data were excellent (r(sp) 0.82-1.00), and dietary intake and feeding patterns correlated well between interviews (r(sp) 0.66-0.99, kappa 0.57-0.95). However, correlations for the frequency and daily intake of specific table foods had a wide range (r(sp) 0.06-0.97). The energy and specific nutrient intakes had high repeatabilities (r(sp) 0.72-0.79). Dog owners were quite consistent in reporting living patterns, exercise and dog-training activities (r(sp) 0.65-0.94, kappa 0.43-0.88), except for number of walks per day (r(sp) 0.50). The repeatabilities also were excellent for the evaluation of health status (r(sp) 0.78-0.99, kappa 0.81-1.00). The questionnaire also was compared to a 7-day weighed record of total food intake and registration of exercise to give data on the validity. The questionnaire was given 62 (S.D. 19) days before the weighed registrations, and the overall response percentage was 76% (58/76). Correlations for the frequency and amount of commercial feeds given were high (0.81-0.92), although correlations for specific table foods had a wider range (0.03-0.81). Correlations for total energy, protein, fat and carbohydrate intakes were between 0.80 and 0.85 in the total diet, and 0.79-0.85 in the commercial part of the diet. The correlations for frequency and amount of exercise ranged between 0.50 and 0.77. Corresponding correlations for training activities (such as hunting, tracking, and obedience) were 0.51-0.68.

Adult↗

Losartan increases renal blood flow during isoflurane anesthesia in sheep.

BACKGROUND: Inhaled anesthetics cause a transient reversible depression of renal function by direct renal effects or indirectly by changes in neurohumoral systems or cardiovascular performance. When the sympathetic nervous activity is decreased during anesthesia, other vasoactive systems like vasopressin (AVP) and particularly the renin angiotensin system (RAS) are of importance for blood pressure maintenance. Little is known about how the renal circulation is affected by angiotensin receptor blockade during isoflurane anesthesia. METHODS: The study was performed on isoflurane anesthetized sheep equipped with flow probes (placed around a femoral and a renal artery) and a pulmonary artery catheter. During stable conditions the sheep were given one or more of the following substances: isotonic saline (NaCl); losartan (LOS) 10 mg x kg(-1); prazosin (PRAZ) 0.2 mg x kg(-1) and a vasopressin V1-receptor antagonist (AVP-a) 10 microg x kg(-1). RESULTS: LOS and AVP-a did not affect mean arterial pressure (MAP), whereas PRAZ lowered MAP significantly (from 98+/-12 to 65+/-7 mmHg). Renal blood flow (RBF) increased after LOS treatment (148+/-34 to 222+/-33 ml x min(-1)). The other substances were without effect on RBF. Femoral blood flow remained unchanged after all treatments. CONCLUSION: We conclude that the sympathoadrenal system is still the major determinant for blood pressure maintenance during isoflurane anesthesia in sheep. The apparently increased activity of the renin angiotensin system in this situation causes a reduction in renal blood flow, which is counteracted by angiotensin II AT1-receptor blockade.

Anesthesia↗

Effects of losartan, prazosin and a vasopressin V1-receptor antagonist on renal and femoral blood flow in conscious sheep.

The regulation of blood flow to different organs is determined by the autonomic nervous system and systemic and/or local vasoactive substances. Although the cardiovascular effects of the renin-angiotensin system (RAS), the sympathoadrenal system and vasopressin (AVP) have been thoroughly studied, there are relatively few investigations on these systems with concomitant measurements of systemic haemodynamics and regional blood flow in conscious unstressed individuals. We therefore studied effects of pharmacological blockade of AVP V1-, angiotensin II (ANG II) AT1-and adrenergic alpha-receptors on central and regional (renal and femoral blood flow) haemodynamics in adult conscious ewes. Eight adult cross-bred ewes were chronically intrumented with peri-vascular ultrasonic flow probes implanted unilaterally around the renal and the femoral artery. While standing in their habitual environment, systemic and regional haemodynamics were measured before and after the following treatments as single intravenous injections. Animals in group A (n = 6) were given isotonic saline (NaCl) followed by the AT1-receptor blocker losartan (LOS, 10 mg kg-1) 30 min later; group B (n = 6) animals were given the alpha-adrenoceptor blocker prazosin (PRAZ, 0.2 mg kg-1); and group C (n = 6) the vasopressin V1 receptor antagonist [d(CH2)5Tyr(Me)AVP] (AVP-a, 10 microg kg-1). PRAZ reduced mean arterial pressure (MAP) by 11% concomitant with an increase in heart rate (HR) (32%), whereas the other substances where without effect on those variables. Femoral blood flow (FBF) was enhanced (increased by 82%) by injection of PRAZ only. Administration of LOS increased the renal blood flow (RBF) by 11% while the other drugs were without effect on that parameter. We conclude that basal renal vascular tone in conscious unstressed sheep is dependent on angiotensinergic mechanism and that blockade of this influence causes a local increase in flow without concomitant effects on systemic haemodynamics.

Angiotensin Receptor Antagonists↗

Demographic data of a population of insured Swedish dogs measured in a questionnaire study.

Dogs, in the age range 1-3 years old, were randomly selected from the largest animal insurance database in Sweden for inclusion in the study. The study was performed in 1997, and a total of 680 dog owners were selected for the study. A total of 461 dog owners completed the survey, at an overall response rate of 68%. Data was compared to a recent gallup performed on a sample of all dogs in Sweden. The demographic statistics of the insured dog population were in many aspects similar to the total dog population of Sweden. Typical for both insured dogs and the total population of dogs were a low proportion of neutered dogs, that many dogs were bought at an early age, that many dogs were in contact with a "breeder" when sold, and a similar profile of health status. However, "dog breeders" seemed to have their dogs insured to a higher extent than the general dog owner. It was concluded that as the populations were alike in many respects, it is reasonable to use the insurance database for epidemiological studies on diet and exercise in Swedish dogs.

Animals↗

Angiotensin II receptor antagonism increases gut oxygen delivery but fails to improve intestinal mucosal acidosis in porcine endotoxin shock.

The renin angiotensin system is highly activated in shock states and has been suggested to be involved in the pathophysiology of the markedly deteriorated splanchnic circulation seen in septic shock. The purpose of the present study was to elucidate the capability of losartan, a nonpeptide angiotensin II type 1 (AT1) receptor antagonist, to attenuate splanchnic blood flow disturbances and counteract intestinal mucosal acidosis in endotoxin shock. A total of 20 pigs were anesthetized and catheterized. Central and regional hemodynamics were monitored. A tonometer in the ileum was used for measurement of mucosal pH. Onset of endotoxin challenge was followed by losartan administration (n = 10) 2 h later. Ten animals receiving endotoxin only served as controls. The experiments were terminated 5 h after onset of endotoxin challenge. Endotoxin infusion induced an hypodynamic shock with a reduction in cardiac index and systemic oxygen delivery. Losartan reduced both systemic vascular resistance and pulmonary capillary wedge pressure while stroke volume was improved. Pulmonary hypertension induced by endotoxin was significantly reduced by losartan without further changes in gas exchange. The profound reduction in gut oxygen delivery in response to endotoxin was counteracted by losartan administration. However, losartan failed to improve the markedly deteriorated intestinal mucosal pH and mucosal-arterial PCO2gap (i.e., difference in intestinal mucosal PCO2 and arterial PCO2). Also the mucosal-portal venous PCO2gap, used as a monitor of the mucosa in relation to the gut as a whole (including the spleen and pancreas), was greatly increased by endotoxemia but unaffected by losartan administration. In summary, although the angiotensin II type 1 receptor antagonist losartan improved gut oxygen delivery and reduced pulmonary hypertension during established endotoxin shock, it had no effect on intestinal mucosal acidosis. These findings suggest contribution of the angiotensin II type 1 receptor to perfusion disturbances, but not to deterioration of intestinal mucosal homeostasis seen during endotoxemia.

Acidosis↗

Effect of individual or combined ablation of the nuclear groups of the lamina terminalis on water drinking in sheep.

The subfornical organ (SFO), organum vasculosum of the lamina terminalis (OVLT), and median preoptic nucleus (MnPO) were ablated either individually or in various combinations, and the effects on drinking induced by either intravenous infusion of hypertonic 4 M NaCl (1.3 ml/min for 30 min) or water deprivation for 48 h were studied. Ablation of either the OVLT or SFO alone did not affect drinking in response to intravenous 4 M NaCl, although combined ablation of these two circumventricular organs substantially reduced but did not abolish such drinking. Ablation of the MnPO or MnPO and SFO together also substantially reduced, but did not abolish, drinking in response to intravenous hypertonic NaCl. Only near-total destruction of the lamina terminalis (OVLT, MnPO, and part or all of the SFO) abolished acute osmotically induced drinking. The large lesions also reduced drinking after water deprivation, whereas none of the other lesions significantly affected such drinking. None of these lesions altered feeding. The results show that all parts of the lamina terminalis play a role in the drinking induced by acute increases in plasma tonicity. The lamina terminalis appears to play a less crucial role in the drinking response after water deprivation than for the drinking response to acute intravenous infusion of hypertonic saline.

Animals↗

Effects of rapid colloid volume expansion on pulmonary microvascular pressure and lung water in the conscious sheep.

Increased pulmonary microvascular pressure (Pmv), in combination with other factors, may cause pulmonary interstitial oedema. Whether increased Pmv alone induces alveolar oedema is questionable. In the present study we used the heavy water-indocyanine green dilution method to measure lung water during a rapid intravascular volume expansion in the sheep. Eight conscious sheep were given two 10-min intravenous infusions of either 50 ml/kg (N = 2) or 35 ml/kg (N = 6) of dextran 60 with an interval of 10 min between them. At a Pmv of 40 mmHg, respiratory distress was observed in sheep no. 2 which had been given a total amount of 100 ml/kg of dextran; this was immediately followed by a lethal pulmonary haemorrhage. Mean Pmv in the remaining seven sheep increased to 31 (7) mmHg in response to the volume expansion without causing any respiratory distress or increase in lung water. These results show that in conscious sheep the lungs have strong protective mechanisms against hydrostatic oedema. They do not support the hypothesis that increased Pmv alone induces alveolar oedema, but suggest that an increase in Pmv to 40 mmHg may cause stress failure of the pulmonary vasculature.

Animals↗

Peroxidase-catalyzed oxidation of 3,5-dimethyl acetaminophen causes cell death by selective protein thiol modification in isolated rat hepatocytes.

In this study we used a peroxidase model system (glucose/glucose oxidase and horseradish peroxidase) to investigate the effect of extracellularly generated reactive metabolites of 3,5-Me2-acetaminophen on cell viability and on cellular thiol levels. Incubation of hepatocytes with 3,5-Me2-acetaminophen in the presence of glucose/glucose oxidase and horseradish peroxidase caused a concentration-dependent loss of cell viability. Loss of viability was associated with decreased protein thiol levels. Addition of the reducing agent DTT, but not catalase, during the incubation restored cellular protein thiol levels and arrested the cell killing. Protein thiol depletion occurred selectively to the mitochondrial and microsomal fractions and was specific for a very limited number of protein bands. The data suggest that the oxidative modification of individual protein cysteine residues within the latter two organelle fractions is critically involved in the mechanism of toxicity.

Acetaminophen↗

Intracerebroventricular angiotensin II increases tolerance to blood loss in conscious sheep.

Intracerebroventricular (i.c.v.) infusion of hypertonic NaCl improves the tolerance to haemorrhage in sheep. Since i.c.v. angiotensin II (ANG II) shares many of the effects of hypertonic NaCl on fluid balance control and blood pressure, we aimed to determine whether i.c.v. ANG II would also be effective in that regard. Six adult conscious ewes were bled from the jugular vein until the mean arterial pressure suddenly dropped to between 45 and 50 mmHg, during an i.c.v. infusion of ANG II (2 pmol kg-1 min-1) which commenced 30 min prior to start of blood removal and continued until end of retransfusion about 80 min after haemorrhage. A corresponding haemorrhage in the same animals during an i.c.v. infusion of 0.9% NaCl served as controls. Significantly more blood had to be withdrawn to induce hypotension when ANG II was given i.c.v. (22.3 +/- 1.8 vs. 12.6 +/- 1.2 mL kg-1). The degree of hypotension and the recovery rate of the blood pressure did not differ between the experiments. The increased tolerance to blood loss by ANG II i.c.v. was accompanied by a reinforced elevation of the systemic vascular resistance and a larger decline of the cardiac output. The plasma norepinephrine concentration was significantly increased immediately after haemorrhage during i.c.v. ANG II, but not in control experiments. The overall vasopressin response to the hypotensive blood loss was not affected by ANG II, but high plasma levels were obtained already during the non-hypotensive stage of haemorrhage. The i.c.v. infusion of ANG II caused a significant lowering of the plasma protein concentration before start of bleeding and accentuated the haemodilution caused by the haemorrhage. We conclude that central administration of ANG II increases the tolerance to haemorrhage in sheep but with concomitant haemodynamic changes which appear unfavourable regarding cardiac load and tissue perfusion.

Angiotensin II↗

Renal function during intravenous infusion of urological irrigating fluids in the sheep.

BACKGROUND: Oliguria or anuria is an important sign of the transurethral resection syndrome, but the mechanism is not clear. METHODS: We gave an intravenous infusion of 40 ml/kg of glycine 1.5%, sorbitol 2%-mannitol 1%, and isotonic saline (control) in 6 conscious ewes and studied if irrigating fluids cause acute disturbances of kidney function. RESULTS: Both the electrolyte-free solutions induced an increase in urine flow and persistent hypo-osmolality. The renal clearances of p-aminohippuric acid and inulin as well as the unilateral renal blood flow, which was measured via ultrasonic flow probes, increased in response to infusion of glycine but not to sorbitol-mannitol. After the infusions, the renal clearances decreased transiently to below baseline levels. Hypertonic saline was given after half of the infusions of electrolyte-free irrigating fluid. This treatment redistributed water from the cells to the extracellular fluid, but had no effect on renal function. CONCLUSIONS: We conclude that 2500 ml of electrolyte-free irrigating fluid had no detrimental effects on kidney function in sheep. The changes we observed were essentially the same as after infusion of isotonic saline.

Animals↗

Angiotensin and the brain.

A brief account for the renal renin-angiotensin system (RAS), its inhibitors and receptors, as for the presence of an intrinsic cerebral RAS is initially provided. The review is then focused upon the circumventricular organs as cerebral targets for blood-borne angiotensin II (Ang II) and on centrally mediated Ang II effects. These concern influences upon the cardiovascular system, water balance, sodium balance, and ACTH-cortisol secretion.

Adrenocorticotropic Hormone↗

Influence of forebrain lesions and isoflurane anaesthesia, respectively, on responses to the intracarotid infusion of angiotensin II in sheep.

In conscious sheep, lesions involving the anterior wall of the third cerebral ventricle extinguished the dipsogenic and cortisol releasing effects of 10 min intracarotid (i.c.) infusions of angiotensin II (Ang II) (20 pmol kg-1 min-1). The sustained hypertension obtained in response to i.c. Ang II in the intact animal was not significantly changed by the forebrain lesions. Pronounced, but short-lasting tachycardia immediately developed in response to i.c. Ang II in control animals. After a 1 min return to initial values the heart rate (HR) rose to about 20 beats min-1 above pre-infusion level during the remaining infusion period. After a brief post-infusion fall, HR retook that level. It then gradually declined but did not return to initial level until about 25 min later. During isoflurane anaesthesia in the latter animals carotid blood pressure (cBP) was reduced by approximately 30% while the HR was more than doubled. The cBP rise in response to i.c. Ang II infusion was < 50% of that seen in awake animals and the pressure returned to initial level within approximately 5 min after the end of the infusion. The infusion did not influence the HR. This study provides support for the idea that blood borne Ang II, bound at cerebral sites posterior to the hypothalamic region, continues to have cardiovascular effects for approximately 20 min after the concentration in the blood has returned to pre-infusion level.

Anesthesia↗

Plasma atrial natriuretic peptide concentration and renin activity during overhydration with 1.5% glycine solution in conscious sheep.

We estimated the changes of fluid compartment volumes and concomitant effects on plasma atrial natriuretic peptide (ANP) and plasma renin activity (PRA) for up to 4 hr after intravenous infusion of 57 ml/kg of 1.5% glycine solution over 40 min in six conscious ewes. Infusions of the same volumes of isotonic saline served as controls. Glycine infusions resulted in a four-fold increase and saline in a doubling of the plasma ANP concentration, despite a more pronounced volume expansion from saline. The ANP level remained significantly elevated for 2 hr after glycine infusion. This result suggests that glycine has a specific ANP-stimulating effect which may contribute to the hypovolemia, hypotension, and natriuresis seen in the "transurethral resection (TUR) syndrome." The PRA decreased by about 50% in response to both infusions. However, PRA returned to the baseline level at the end of the glycine infusion, whereas it remained depressed during the entire follow-up period after saline infusion. This is in accordance with a pure volumetric influence on renin release, since calculations of fluid distribution between different compartments suggested that, in contrast to the effect of saline, only a small amount of irrigant water remained in the extracellular fluid after glycine administration. The urea and creatinine clearances increased only in response to isotonic saline. Glycine infusion was even followed by reduction of the creatinine clearance.

Analysis of Variance↗

Centrally mediated influences of hypertonic NaCl and angiotensin II on regional blood flow and hemodynamic responses to hypotensive hemorrhage in conscious sheep.

The influence of separate and combined intracerebroventricular (ICV) infusions of hypertonic (.5 M) NaCl (HTNa) at .02 mL min-1 and angiotensin II (ANG II) at 1 pmol kg-1 min-1 on tolerance to hemorrhage, accompanying systemic hemodynamic changes, and regional blood flow was studied in adult conscious sheep. Corresponding measurements during ICV .9% NaCl served as controls. The hemorrhage volume needed to lower the blood pressure to about 50 mmHg was significantly larger during treatment with HTNa and HTNa/ANG II (27.8 +/- 2.2 and 28.3 +/- 2.5 mL kg-1, respectively; p < .001; about 45% of estimated blood volume) as well as during ANG II (20.1 +/- 1.3 mL kg-1; p < .01) compared to controls (15.1 +/- .7 mL kg-1; about 25% of estimated blood volume). In spite of a larger hemorrhage volume, the lowering of the cardiac output was not accentuated, and its subsequent recovery was not impaired during ICV infusion of HTNa or HTNa/ANG II. Similarly, the posthemorrhage restoration of the systemic blood pressure was not negatively affected by the more pronounced hypovolemia induced during the ICV treatments compared to controls. In contrast to ANG II, HTNa infusion, alone or in combination with ANG II, was accompanied by a significantly lower renal blood flow, and a higher renovascular resistance, during the posthemorrhage period. The femoral blood flow was maintained or even slightly elevated after hemorrhage in all experiments. The integrated results of the study imply differentiated hemodynamic effects of centrally administered HTNa and ANG II.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗